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Phenylbutazone: ‘Butazolidin’
1066
Book Reviews
From those general criticisms the author passes to the subject of pain in medicine. At a certain stage in his career every student or doctor discovers the reality of the problem of pain. He finds out what pain does to the body and mind-its pathological and personal effects. Pain is “the mystery which can’t be paralleled in the world of this life. It is an evil placed in opposition to life, an obstacle and a threat which throws man aside, like someone who dies a thousand times over. To a patient in pain, the doctor at the bedside becomes a rare and mysterious light. It contains its meaning hidden in the apparent senselessness of the world.” The ordinary person, says BU~~ENDIJK,cannot explain pain and experience offers no adequate reason. We can accept the fact that we have to die once and death can come suddenly. But chronic pain is felt repeatedly and only when we are conscious. BUYTENDIJK writes of the “clear light of thoughtlessness which characterizes a life free of pain.” On the other hand “in the darkness of his pain, man is alone; he is broken inwardly, isolated within his suffering body, and in this state he discovers something new: existing.” Pity felt for the suffering, says BUYTENDIJK, is the usual impulse of the doctor; but pity continues as a motive only as long as it is still inspired by clear insight into the nature of man and the purpose of his suffering. As soon as we start to lose patience with the sufferer our pity is useless: Many a sick person has ao need of words to prove that he has found the true answer to the true question since the existential purpose of pain has been fulfilled by his serene composure and patience in union with Christ the ‘Man of Sorrows’. MICHAEL KELLY
PHENYLBUTAZONE: ‘BUTAZOLIDIN’. H. J. VON RECHENBERG(Foreword Edward Arnold Ltd., London, 1962. 2nd Edition. 201 pp. Price 30s.
by 0. GSELL).
PROFESSOR0. GSELL and Dr. H. .I. VON RECHENBERGof Basle were the first doctors to make clinical observations on the antirheumatic effects of phenylbutazone. Like many other important medical discoveries, the synthesis of phenylbutazone came from a lucky chance. Amidopyrine when swallowed is a painkiller equal in strength to aspirin. GSELL and VON RECHENBERGwondered if when injected it would have stronger analgesic effects. But amidopyrine is completely insoluble in all the usual solvents, and it could not even be prepared as a suspension. GSELL approached the firm of Geigy and asked them to get amidopyrine into solution in whatever way they could. Geigy scientist Mr. H. STENZL was put in charge of the job of solutilizing amidopyrine. The easiest way was to mix amidopyrine with an equal amount of a supposedly inert material STENZL had synthesized, then dissolve the two in an alcoholic solution. This mixture-alled Irgapyrin-was put up in ampoules of 1000 mg, with 500 mg each of amidopyrine and the ‘inert’ material. GSELL and VON RECHENBERCinjected it into a rmmber of rheumatic patients and discovered it had an analgesic effect much greater than the effect of amidopyrine tablets. Furthermore, the effect of Irgapyrin was delayed 12-24 hours, whereas the aspirin-like effect of amidopyrine appears within l-2 hours. The effect of Irgapyrin on some rheumatic patients was of a different qualitv-almost like the effect of cortisone. GSELL and VON RECHEN~ERGgot the help of a number of rheumatologists in Basle and Zurich. All reported antirheumatic effects like those of cortisone. The obvious deduction was that the effects did not come from amidopyrine but from something new. The supposedly inert substance must be the active agent. STENZL called this phenylbutazone; then he had to purify it, dissolve it in alcohol, and put it up in ampoules for injection. Then 500 mg was found to equal 1000 mg of Irgapyrin in effect. Fifteen years ago doctors were used to giving most of their useful drugs by injection. Insulin and penicillin being destroyed in the stomach, we had come to accept the inconvenient method of injection for a great many other products. Cortisone suspension was injected for a year before a doctor decided to risk wasting a dose to see if it would be absorbed from the stomach. From then on the menace of the steroids was multiplied tenfold. And the same happened with phenylbutazone. The Basle team got CURRIE of Glasgow and KUZELL of San Francisco to inject phenylbutazone into their rheumatic patients. They reported good effects; then they suggested that tablets of phenylbutazone be given. Soon there was no doubt that phenylbutazone tablets were more reliable than the injections. At first phenylbutazone was given in doses too large and toxic effects were reported. VON RECHENBERGand the manufacturers did not hush these up. On the contrary they- emphasized almost from the beginning that doses should not be greater than 400 mg daily, that phenylbutazone should be withdrawn when toxic effects appear, that it should not be given to the aged or to people with gastric ulcers or heart disease.
Book Reviews
1067
The manufacturers authorized BERNARDBRODIE of Bethesda, Md. to find out what phenylbutazone did to the body and to look for metabolites which might be more valuable than phenylbutazone itself. BRODIE’Sdiscovery of oxyphenbutazone was almost like a whodunit. Then it was capped with the equally astonishing job of synthesizing oxyphenbutazone by Geigy in Basle. A good deal of this book goes to prove that we still do not know how phenylbutazone suppresses rheumatic inflammation. There are 1690 references occupying 39 pages, and a good index. Chapter I deals with chemistry, Chapter II with biochemistry and Chapter III with pharmacology. Before any clinical effects we read 63 pages about the effects of phenylbutazone on phosphorus and purine metabolism, SH-activators, hyaluronidase, effects on experimental inflammation, analgesic effects on animals, effects on animals’ hearts, kidney, liver. etc. We cannot discover the effects of phenylbutazone because we are trying too hard. Animal experiments are notoriously unreliable when we try to find anything about the human body. VON RECHENBERG is extremely conscientious and devotes 62 pages to toxic effects. Contrariwise, only 11 pages discuss this remarkable new antirheumatic drug which takes 24 hours to act. It has meant a new outlook for doctors who treat rheumatism and a new life for 40 per cent of all rheumatic patients. The 62 of 150 pages of script devoted to toxic effects are out of proportion. VON RFXHENBERG quotes his own preface to the first edition: “Its merits appear to slightly outweigh its demerits, even though on occasions the scales appear to tremble in the balance.” In that the author was quoting verbatim from a 1953 statement by DUDLEY HART of London. Since then HART has written many papers in which he has indicated that phenylbutazone’s merits greatly outweigh its demerits. In a book about a drug alleged to relieve rheumatic disease, we should expect clinical details of rheumatic patients treated over the years. That is typical of today’s medicine; the clinician has an inferiority complex in front of the test tube. A drug with outstanding clinical effects has only eleven pages devoted to the effects and the rest of the book is taken up with inconclusive experiments. The drug’s action is unknown; therefore we need the eye of a visionary to rdiscem which of the numerous biochemical facts is significant and which is not. Phenylbutazone is a specifically antirheumatic drug; in its effect on rheumatic inflammatory lesions it behaves like no other drugs except oxyphenbutazone and indomethacin. Phenylbutazone is relatively safe if the contra-indications are observed, if the daily dose does not ,exceed 400 mg. and if it is withdrawn as soon as undesirable symptoms appear. The commencing dose is often 300 mg and in older people 200 mg. It is cumulative; intermittent treatment is best; patients should stop for one or two days a week. Relapses are caused by an unresponsive state; this can be overcome by stopping treatment for a few days and starting again with the same dose. Perseverance is required to get the best value from phenylbutazone. The treatment should never be abandoned merely because the patient has had a relapse. The wrong way to treat a relapse under phenylbutazone is to increase the dose forthwith without interrupting treatment. Most of the recorded cases of severe toxicity were caused either by overdosage or by administration of phenylbutazone to unsuitable patients, or to persistence with medication after the appearance of toxic symptoms. Some of the doctors who tried phenylbutazone early would not persevere with it because it did not lower the sedimentation rate of the patients who claimed to be cured. The reasonable deduction from this is that we should no longer rely on the sedimentation rate. But the rheumatologists, because of the sedimentation rate, called phenylbutazone not antirheumatic. but ‘anti-inflammatory’. This is an unscientific and meaningless word. Time has proved phenylbutazone the first specifically antirheumatic drug. The lesson to be learned from phenylbutazone is that the patient as a whole is a great deal more important than the minute data which we learn with microscope and test tube. Phenylbutazone provides the medical profession with a prime lesson in the value of clinical assessment of the patient; the history matters most; physical examination of the patient matters next; chemical tests do not matter. MICHAEL KELLY MEDICAL INQUIRIES AND OBSERVATIONS UPON DISEASES OF THE MIND, 1812. BENJAMINRUSH (17451813), with an introduction by S. BERNARDWORTIS. Hafner Publishing Inc., New York, 1962. 367 pp. Price $2.75. THE Library Publications Committee of the New York Academy of Medicine should be thanked for authorizing the production of a fascimile copy of BENJAMINRUSH’S best piece of writing. RUSH did not write on mental diseases as a specialist but as a physician with a broad outlook on medicine and true interest in his patients. That is why this book is more readable
Book Reviews
From those general criticisms the author passes to the subject of pain in medicine. At a certain stage in his career every student or doctor discovers the reality of the problem of pain. He finds out what pain does to the body and mind-its pathological and personal effects. Pain is “the mystery which can’t be paralleled in the world of this life. It is an evil placed in opposition to life, an obstacle and a threat which throws man aside, like someone who dies a thousand times over. To a patient in pain, the doctor at the bedside becomes a rare and mysterious light. It contains its meaning hidden in the apparent senselessness of the world.” The ordinary person, says BU~~ENDIJK,cannot explain pain and experience offers no adequate reason. We can accept the fact that we have to die once and death can come suddenly. But chronic pain is felt repeatedly and only when we are conscious. BUYTENDIJK writes of the “clear light of thoughtlessness which characterizes a life free of pain.” On the other hand “in the darkness of his pain, man is alone; he is broken inwardly, isolated within his suffering body, and in this state he discovers something new: existing.” Pity felt for the suffering, says BUYTENDIJK, is the usual impulse of the doctor; but pity continues as a motive only as long as it is still inspired by clear insight into the nature of man and the purpose of his suffering. As soon as we start to lose patience with the sufferer our pity is useless: Many a sick person has ao need of words to prove that he has found the true answer to the true question since the existential purpose of pain has been fulfilled by his serene composure and patience in union with Christ the ‘Man of Sorrows’. MICHAEL KELLY
PHENYLBUTAZONE: ‘BUTAZOLIDIN’. H. J. VON RECHENBERG(Foreword Edward Arnold Ltd., London, 1962. 2nd Edition. 201 pp. Price 30s.
by 0. GSELL).
PROFESSOR0. GSELL and Dr. H. .I. VON RECHENBERGof Basle were the first doctors to make clinical observations on the antirheumatic effects of phenylbutazone. Like many other important medical discoveries, the synthesis of phenylbutazone came from a lucky chance. Amidopyrine when swallowed is a painkiller equal in strength to aspirin. GSELL and VON RECHENBERGwondered if when injected it would have stronger analgesic effects. But amidopyrine is completely insoluble in all the usual solvents, and it could not even be prepared as a suspension. GSELL approached the firm of Geigy and asked them to get amidopyrine into solution in whatever way they could. Geigy scientist Mr. H. STENZL was put in charge of the job of solutilizing amidopyrine. The easiest way was to mix amidopyrine with an equal amount of a supposedly inert material STENZL had synthesized, then dissolve the two in an alcoholic solution. This mixture-alled Irgapyrin-was put up in ampoules of 1000 mg, with 500 mg each of amidopyrine and the ‘inert’ material. GSELL and VON RECHENBERCinjected it into a rmmber of rheumatic patients and discovered it had an analgesic effect much greater than the effect of amidopyrine tablets. Furthermore, the effect of Irgapyrin was delayed 12-24 hours, whereas the aspirin-like effect of amidopyrine appears within l-2 hours. The effect of Irgapyrin on some rheumatic patients was of a different qualitv-almost like the effect of cortisone. GSELL and VON RECHEN~ERGgot the help of a number of rheumatologists in Basle and Zurich. All reported antirheumatic effects like those of cortisone. The obvious deduction was that the effects did not come from amidopyrine but from something new. The supposedly inert substance must be the active agent. STENZL called this phenylbutazone; then he had to purify it, dissolve it in alcohol, and put it up in ampoules for injection. Then 500 mg was found to equal 1000 mg of Irgapyrin in effect. Fifteen years ago doctors were used to giving most of their useful drugs by injection. Insulin and penicillin being destroyed in the stomach, we had come to accept the inconvenient method of injection for a great many other products. Cortisone suspension was injected for a year before a doctor decided to risk wasting a dose to see if it would be absorbed from the stomach. From then on the menace of the steroids was multiplied tenfold. And the same happened with phenylbutazone. The Basle team got CURRIE of Glasgow and KUZELL of San Francisco to inject phenylbutazone into their rheumatic patients. They reported good effects; then they suggested that tablets of phenylbutazone be given. Soon there was no doubt that phenylbutazone tablets were more reliable than the injections. At first phenylbutazone was given in doses too large and toxic effects were reported. VON RECHENBERGand the manufacturers did not hush these up. On the contrary they- emphasized almost from the beginning that doses should not be greater than 400 mg daily, that phenylbutazone should be withdrawn when toxic effects appear, that it should not be given to the aged or to people with gastric ulcers or heart disease.
Book Reviews
1067
The manufacturers authorized BERNARDBRODIE of Bethesda, Md. to find out what phenylbutazone did to the body and to look for metabolites which might be more valuable than phenylbutazone itself. BRODIE’Sdiscovery of oxyphenbutazone was almost like a whodunit. Then it was capped with the equally astonishing job of synthesizing oxyphenbutazone by Geigy in Basle. A good deal of this book goes to prove that we still do not know how phenylbutazone suppresses rheumatic inflammation. There are 1690 references occupying 39 pages, and a good index. Chapter I deals with chemistry, Chapter II with biochemistry and Chapter III with pharmacology. Before any clinical effects we read 63 pages about the effects of phenylbutazone on phosphorus and purine metabolism, SH-activators, hyaluronidase, effects on experimental inflammation, analgesic effects on animals, effects on animals’ hearts, kidney, liver. etc. We cannot discover the effects of phenylbutazone because we are trying too hard. Animal experiments are notoriously unreliable when we try to find anything about the human body. VON RECHENBERG is extremely conscientious and devotes 62 pages to toxic effects. Contrariwise, only 11 pages discuss this remarkable new antirheumatic drug which takes 24 hours to act. It has meant a new outlook for doctors who treat rheumatism and a new life for 40 per cent of all rheumatic patients. The 62 of 150 pages of script devoted to toxic effects are out of proportion. VON RFXHENBERG quotes his own preface to the first edition: “Its merits appear to slightly outweigh its demerits, even though on occasions the scales appear to tremble in the balance.” In that the author was quoting verbatim from a 1953 statement by DUDLEY HART of London. Since then HART has written many papers in which he has indicated that phenylbutazone’s merits greatly outweigh its demerits. In a book about a drug alleged to relieve rheumatic disease, we should expect clinical details of rheumatic patients treated over the years. That is typical of today’s medicine; the clinician has an inferiority complex in front of the test tube. A drug with outstanding clinical effects has only eleven pages devoted to the effects and the rest of the book is taken up with inconclusive experiments. The drug’s action is unknown; therefore we need the eye of a visionary to rdiscem which of the numerous biochemical facts is significant and which is not. Phenylbutazone is a specifically antirheumatic drug; in its effect on rheumatic inflammatory lesions it behaves like no other drugs except oxyphenbutazone and indomethacin. Phenylbutazone is relatively safe if the contra-indications are observed, if the daily dose does not ,exceed 400 mg. and if it is withdrawn as soon as undesirable symptoms appear. The commencing dose is often 300 mg and in older people 200 mg. It is cumulative; intermittent treatment is best; patients should stop for one or two days a week. Relapses are caused by an unresponsive state; this can be overcome by stopping treatment for a few days and starting again with the same dose. Perseverance is required to get the best value from phenylbutazone. The treatment should never be abandoned merely because the patient has had a relapse. The wrong way to treat a relapse under phenylbutazone is to increase the dose forthwith without interrupting treatment. Most of the recorded cases of severe toxicity were caused either by overdosage or by administration of phenylbutazone to unsuitable patients, or to persistence with medication after the appearance of toxic symptoms. Some of the doctors who tried phenylbutazone early would not persevere with it because it did not lower the sedimentation rate of the patients who claimed to be cured. The reasonable deduction from this is that we should no longer rely on the sedimentation rate. But the rheumatologists, because of the sedimentation rate, called phenylbutazone not antirheumatic. but ‘anti-inflammatory’. This is an unscientific and meaningless word. Time has proved phenylbutazone the first specifically antirheumatic drug. The lesson to be learned from phenylbutazone is that the patient as a whole is a great deal more important than the minute data which we learn with microscope and test tube. Phenylbutazone provides the medical profession with a prime lesson in the value of clinical assessment of the patient; the history matters most; physical examination of the patient matters next; chemical tests do not matter. MICHAEL KELLY MEDICAL INQUIRIES AND OBSERVATIONS UPON DISEASES OF THE MIND, 1812. BENJAMINRUSH (17451813), with an introduction by S. BERNARDWORTIS. Hafner Publishing Inc., New York, 1962. 367 pp. Price $2.75. THE Library Publications Committee of the New York Academy of Medicine should be thanked for authorizing the production of a fascimile copy of BENJAMINRUSH’S best piece of writing. RUSH did not write on mental diseases as a specialist but as a physician with a broad outlook on medicine and true interest in his patients. That is why this book is more readable